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Randomized, Double-blind, Placebo-controlled Phase 3 Study of Ibrutinib, a Bruton's Tyrosine Kinase (BTK) Inhibitor, in Combination With Bendamustine and Rituximab (BR) in Subjects With Relapsed or Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

Phase 3
18 Years
Open (Enrolling)
Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma

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Trial Information

Randomized, Double-blind, Placebo-controlled Phase 3 Study of Ibrutinib, a Bruton's Tyrosine Kinase (BTK) Inhibitor, in Combination With Bendamustine and Rituximab (BR) in Subjects With Relapsed or Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

This is a randomized (individuals will be assigned by chance to study treatments),
double-blind (individuals and study personnel will not know the identity of study
treatments), placebo (an inactive substance that is compared with a drug to test whether the
drug has a real effect in a clinical trial)-controlled study to determine the benefits and
risks of combining ibrutinib and bendamustine and rituximab (BR) in patients with relapsed
or refractory CLL/SLL following at least 1 line of prior systemic therapy. Approximately 580
patients will be randomized in a 1:1 ratio to either treatment arm A (placebo) or treatment
arm B (ibrutinib 420 mg). Study medication will be administered orally once daily on a
continuous schedule. All patients will receive BR as the background therapy plus either
ibrutinib or placebo for a maximum of 6 cycles, after which treatment with ibrutinib or
placebo will continue until disease progression or unacceptable toxicity. A treatment cycle
will be defined as 28 days. The study will include a screening phase, a treatment phase, and
a follow-up phase. Study end is defined as when either 80% of the patients have died or 4
years after the last patient is randomized into the study, whichever occurs first. One
interim analysis is planned for the study. Efficacy evaluations will include computed
tomography scans, laboratory testing, focused physical examinations, bone marrow biopsy and
aspirate, and assessment of patient-reported outcomes. In both treatment arms, samples for
the development of a population-based pharmacokinetic (PK; study of what the body does to a
drug) approach will be collected. Safety will be assessed throughout the study.

Inclusion Criteria:

- Diagnosis of chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL)
that meets protocol-defined criteria

- Active disease meeting at least 1 of the International Workshop on Chronic
Lymphocytic Leukemia 2008 criteria for requiring treatment

- Measurable nodal disease by computed tomography

- Relapsed or refractory CLL or SLL following at least 1 prior line of systemic therapy
consisting of at least 2 cycles of a chemotherapy-containing regimen

- Eastern Cooperative Oncology Group Performance Status score of 0 or 1

- Hematology and biochemical values within protocol-defined limits within 7 days prior
to randomization

- Agrees to protocol-defined use of effective contraception

- Women of childbearing potential must have negative blood or urine pregnancy test at

Exclusion Criteria:

- Recent therapeutic interventions within 3 (chemotherapy/radiotherapy) to 10 weeks

- Prior treatment with ibrutinib or other Bruton's tyrosine kinase inhibitors or prior
randomization in any other clinical study evaluating ibrutinib

- The presence of deletion of the short arm of chromosome 17

- Patients previously treated with a bendamustine-containing regimen who did not
achieve a response or who relapsed within 24 months of treatment with that regimen

- Patients for whom the goal of therapy is tumor debulking prior to stem cell

- Received a hematopoietic stem cell transplant

- Known central nervous system leukemia/lymphoma or Richter's transformation

- Patients with uncontrolled autoimmune hemolytic anemia or autoimmune thrombocytopenia

- Chronic use of corticosteroids

- History of prior malignancy, except: malignancy treated with curative intent and with
no known active disease present for >=3 years before randomization; adequately
treated non-melanoma skin cancer or lentigo maligna without evidence of disease;
adequately treated cervical carcinoma in situ without evidence of disease

- History of stroke or intracranial hemorrhage within 6 months prior to randomization;
or clinically significant cardiovascular disease

- Requires anticoagulation with warfarin or equivalent vitamin K antagonists or
treatment with strong CYP3A4/5 inhibitors

- Known history of human immunodeficiency virus or hepatitis C, or active infection
with hepatitis B or C

- Any uncontrolled active systemic infection or any life-threatening illness, medical
condition, or organ system dysfunction which, in the investigator's opinion, could
compromise the patient's safety, interfere with the absorption or metabolism of
ibrutinib capsules, or put the study outcomes at undue risk

- A woman who is pregnant or breast feeding, or a man who plans to father a child while
enrolled in this study or within 3 months after the last dose of study drug

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Outcome Measure:

Progression-free survival

Outcome Time Frame:

Up to 4 years after the last patient is randomized

Safety Issue:


Principal Investigator

Janssen Research & Development, LLC Clinical Trial

Investigator Role:

Study Director

Investigator Affiliation:

Janssen Research & Development, LLC


United States: Food and Drug Administration

Study ID:




Start Date:

September 2012

Completion Date:

March 2018

Related Keywords:

  • Chronic Lymphocytic Leukemia
  • Small Lymphocytic Lymphoma
  • Chronic lymphocytic leukemia
  • Small lymphocytic lymphoma
  • Relapsed or refractory chronic lymphocytic leukemia
  • Relapsed or refractory small lymphocytic lymphoma
  • Ibrutinib
  • PCI-32765
  • JNJ-54179060
  • Bruton's tyrosine kinase inhibitor
  • Bendamustine
  • Rituximab
  • Leukemia
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Leukemia, Lymphoid
  • Lymphoma



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